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We present a versatile grid reactor setup for transmission electron microscopy (TEM), which is able to track catalytic conversion on TEM amounts of sample. It is based on the concept of decoupling catalytic gas-phase reactions from the structural analysis of identical particles before and after reaction. The system has superior properties in terms of image resolution and long-term measurements compared to conventional in situ TEM analysis. Monitoring catalytic conversions on a TEM grid is enabled by proton-transfer reaction mass spectrometry. In addition, identical location imaging benefits from a secure transfer of the sample between TEM and the reactor system by vacuum transfer holders. Using Pt and Cu/ZnO/Al 2 O 3 as an example we show that structural changes of identical particles or areas of a Pt foil before and after reactive experiments can be tracked. During catalytic testing the samples are exposed to homogeneous reaction conditions. The concept minimizes electron-sample and electron-atmosphere interactions and can prospectively be considered as complementary tool to in situ TEM analysis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: To conduct an audit of teledermatologist expert skin advice, a store and forward tele-dermatological service, to determine its effectiveness and user satisfaction in managing cutaneous adverse drug reactions in patients with hepatitis C, and to demonstrate a unique collaborative model of care for patients receiving specialised drug therapy., Methods: A retrospective analysis of data on teledermatologist expert skin advice referrals from January 2014 to December 2015 was performed. The primary outcomes assessed included number of referrals, referral locations, diagnoses, response times, quality of clinical information provided and user satisfaction ratings., Results: Altogether 43 consultations from 29 referring sites were received from Australian metropolitan and rural settings. Of the patients, 43 were diagnosed with an adverse drug reaction related to the use of either telaprevir or simeprevir. The average time taken for the dermatologist to reply electronically with a final diagnosis and management plan was 1 h 57 min. As many as 26% of referrals required additional photos to establish a diagnosis due to poor-quality images or insufficient detail. Altogether 18 clinicians completed the customer satisfaction survey, all of whom rated teledermatologist expert skin advice nine or above on a scale of one to 10., Conclusions: Teledermatologist expert skin advice was regarded by clinicians as a valuable patient care service. The platform is a novel modality that supports patients undergoing specialised treatments at risk of cutaneous adverse drug reaction., (© 2018 The Australasian College of Dermatologists.)

Although quasi-amorphous iridium oxohydroxides have been identified repeatedly as superior electrocatalysts for the oxygen evolution reaction (OER), an exact description of the performance-relevant species has remained a challenge. In this context, we report the characterization of hydrothermally prepared iridium(III/IV) oxohydroxides that exhibit exceptional OER performances. Holes in the O 2p states of the iridium(III/IV) oxohydroxides result in reactive O I- species, which are identified by characteristic near-edge X-ray absorption fine structure (NEXAFS) features. A prototypical titration reaction with CO as a probe molecule shows that these O I- species are highly susceptible to nucleophilic attack at room temperature. Similarly to the preactivated oxygen involved in the biological OER in photosystem II, the electrophilic O I- species evidenced in the iridium(III/IV) oxohydroxides are suggested to be precursors to species involved in the O-O bond formation during the electrocatalytic OER. The CO titration also highlights a link between the OER performance and the surface/subsurface mobility of the O I- species. Thus, the superior electrocatalytic properties of the iridium (III/IV) oxohydroxides are explained by their ability to accommodate preactivated electrophilic O I- species that can migrate within the lattice., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To conduct an audit of the Skin Emergency Telemedicine Service at Princess Alexandra Hospital in Brisbane from January to December 2014, and determine whether there has been any change in the number, type and location of referrals., Methods: Retrospective analyses of referrals to the teledermatology service were conducted and compared with the 2012 audit. Main outcomes assessed included the number of referrals, referral site location, telediagnosis categories, image characteristics and response times., Results: In 2014, 318 cases were referred to the teledermatology service. The highest number of cases (n = 140) were referred from Princess Alexandra Hospital and Queen Elizabeth II Jubilee Hospital emergency departments. However, referrals to the teledermatology service came from as far as 1600 km distant from Brisbane. The most common provisional telediagnoses were dermatitis or eczema, skin infection or drug eruption. Over half of all referrals (62%) received a response within 3 h and a further 20% were responded to within 3-6 h. Almost half all referring doctors (48%) attached very large image files (> 500 kb) to their referral., Conclusions: The Skin Emergency Telemedicine Service has proved to be a successful, sustainable and valuable addition to the specialist dermatology services provided across Queensland. With adequate funding and resources and appropriate attention to ethical and legal considerations, our service could significantly change the management of Queenslanders with acute skin conditions., (© 2015 The Australasian College of Dermatologists.)

Crystallographic defects play a key role in determining the properties of crystalline materials. The new class of two-dimensional materials, foremost graphene, have enabled atomically resolved studies of defects, such as vacancies,1-4 grain boundaries,(5-7) dislocations,(8,9) and foreign atom substitutions.(10-14) However, atomic resolution imaging of implanted self-interstitials has so far been reported neither in any three-dimensional nor in any two-dimensional material. Here, we deposit extra carbon into single-layer graphene at soft landing energies of ∼ 1 eV using a standard carbon coater. We identify all the self-interstitial dimer structures theoretically predicted earlier,(15-17) employing 80 kV aberration-corrected high-resolution transmission electron microscopy. We demonstrate accumulation of the interstitials into larger aggregates and dislocation dipoles, which we predict to have strong local curvature by atomistic modeling, and to be energetically favorable configurations as compared to isolated interstitial dimers. Our results contribute to the basic knowledge on crystallographic defects and lay out a pathway into engineering the properties of graphene by pushing the crystal into a state of metastable supersaturation.

We report the formation and characterization of boron nitride atomic chains. The chains were made from hexagonal boron nitride sheets using the electron beam inside a transmission electron microscope. We find that the stability and lifetime of the chains are significantly improved when they are supported by another boron nitride layer. With the help of first-principles calculations, we prove the heteroatomic structure of the chains and determine their mechanical and electronic properties. Our study completes the analogy between various boron nitride and carbon polymorphs, in accordance with earlier theoretical predictions.

Graphitic carbon nitride has been predicted to be structurally analogous to carbon-only graphite, yet with an inherent bandgap. We have grown, for the first time, macroscopically large crystalline thin films of triazine-based, graphitic carbon nitride (TGCN) using an ionothermal, interfacial reaction starting with the abundant monomer dicyandiamide. The films consist of stacked, two-dimensional (2D) crystals between a few and several hundreds of atomic layers in thickness. Scanning force and transmission electron microscopy show long-range, in-plane order, while optical spectroscopy, X-ray photoelectron spectroscopy, and density functional theory calculations corroborate a direct bandgap between 1.6 and 2.0 eV. Thus TGCN is of interest for electronic devices, such as field-effect transistors and light-emitting diodes., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Quantum dots (QDs) coated with an albumin-derived copolymer shell exhibit significant photoresponsiveness to DNA loading and have great potential for investigating gene delivery processes. The QDs reported herein are positively charged, have attractive optical properties, and are noncytotoxic and notably stable in live cells. Their complex formation with plasmid DNA leads to proportionally decreased photoluminescence and efficient gene transfection is observed. Therefore, they are suitable for live-cell bioimaging and mechanistic studies of nonviral gene delivery. Fluorescence correlation spectroscopy is applied for the first time to investigate individual QDs diffusing in large endosomes inside living cells, and serves as a valuable tool to study the physical properties of QDs inside live cells. The data obtained in this study strongly support the notable stability of these QDs, even in cell endosomes., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background/objectives: The Reed naevus or pigmented spindle cell naevus of Reed (PSCN) was previously considered a pigmented variant of the spindle cell-type of Spitz naevus. It is now considered a distinct entity and may overlap with cutaneous melanoma in both clinical and dermatoscopic features. We hypothesised that PSCN is an under-recognised entity in Australia and present a typical case. To test our hypothesis, we performed a clinically based survey of Australian dermatology trainees (Registrars). A further aim of our study was to determine the approach of dermatology trainees in this country to the management of this type of lesion., Methods: A web-based survey questionnaire based on the presented case was circulated to trainees of the Australasian College of Dermatologists. Responses, including level of training and initial approach to management, were collated and form the basis of the results presented herein., Results: Of 39 respondents, 13 (33%) diagnosed the lesion as PSCN. The majority (33/39; 84.6%) indicated they would biopsy the lesion, with most of these (91%) preferring excisional biopsy., Conclusions: The results support our hypothesis that PSCN is under-recognised in Australia. The results also show that despite difficulty distinguishing this lesion, management of these lesions by dermatology trainees in Australia is consistent and parallels current recommendations., (© 2011 The Authors. Australasian Journal of Dermatology © 2011 The Australasian College of Dermatologists.)

The electronic charge density distribution or the electrostatic atomic potential of a solid or molecule contains information not only on the atomic structure, but also on the electronic properties, such as the nature of the chemical bonds or the degree of ionization of atoms. However, the redistribution of charge due to chemical bonding is small compared with the total charge density, and therefore difficult to measure. Here, we demonstrate an experimental analysis of charge redistribution due to chemical bonding by means of high-resolution transmission electron microscopy (HRTEM). We analyse charge transfer on the single-atom level for nitrogen-substitution point defects in graphene, and confirm the ionicity of single-layer hexagonal boron nitride. Our combination of HRTEM experiments and first-principles electronic structure calculations opens a new way to investigate electronic configurations of point defects, other non-periodic arrangements or nanoscale objects that cannot be studied by an electron or X-ray diffraction analysis.

Objective: To investigate the safety and efficacy of a special terpene combination in the treatment of patients with urolithiasis after extracorporeal shockwave lithotripsy (ESWL)., Patients and Methods: 222 patients with clinically stable kidney or ureter stones of 0.3-2.0 cm undergoing complication-free ESWL were randomised to receive a special terpene combination (Rowatinex®; 3 × 2 capsules/day) or placebo. The study consisted of a 12-week active treatment phase and a 2-week follow-up phase. All patients had a physical examination, and diagnosis of kidney stones was made by X-ray, intravenous pyelogram or ultrasound at weeks 1, 4, 8 and 12 as well as after 2 weeks of follow-up. Stone-free status was defined as obviously successful expulsion of calculi/fragments, being without any stone., Results: In all, when compared to placebo, significantly more patients receiving the terpene combination treatment in the intent-to-treat (ITT) group [72 (67.9%) vs. 49 (50.0%); p = 0.0009] and the per-protocol (PP) group [69 (78.4%) vs. 48 (52.2%); p = 0.0004] were stone-free at the end of the study. Treatment with the terpene combination was also more effective when analysed with respect to the size of the treated stone. In addition, treatment with the terpene combination significantly reduced the median time to stone-free status from 85.0 to 56.0 days (p = 0.0061) and from 85.0 to 49.5 days (p = 0.0028) in the ITT and PP populations, respectively. Nine mild-to-moderate adverse events (AE; terpene combination group: 7 AE in 4 patients; placebo group: 2 AE in 2 patients) were assessed as drug-related., Conclusions: Treatment with the terpene combination is well tolerated and safe. The terpene combination was found to be an efficacious treatment in eliminating calculi fragments generated by ESWL as compared to placebo. The pharmacodynamic properties of the terpene combination (antilithogenic, antibacterial, antiinflammatory, spasmolytic and analgesic effects), which have been also confirmed in preclinical studies, represent a valuable alternative to the different drugs used in the treatment of urolithiasis., (Copyright © 2010 S. Karger AG, Basel.)

Objectives: To evaluate the safety of two applications of PEP005 (ingenol mebutate) gel in superficial basal cell carcinoma. Efficacy was a secondary end-point., Methods: Randomized, vehicle-controlled, phase IIa study conducted at eight private dermatology clinics in Australia. A total of 60 patients with histologically confirmed superficial basal cell carcinoma (lesion size, 4-15 mm) were randomized to treatment on days 1 and 2 (Arm A) or days 1 and 8 (Arm B) and, within each arm, to ingenol mebutate gel, 0.0025%, 0.01% or 0.05%, or vehicle gel. The main outcome measures were the incidence and severity of adverse events and local skin responses in Arms A and B; lesion clearance at day 85 was a secondary measure., Results: The incidence of adverse events was low. One patient treated with ingenol mebutate gel, 0.05% in Arm A experienced severe flaking/scaling/dryness extending beyond the application site. Non-severe, potentially treatment-related events included erythema extending beyond the application site, application-site pain and headache in two patients each. Six patients in Arm A had one or more severe local skin responses. Efficacy appeared to be dose-related and there was a trend towards higher clinical and histological lesion clearance rates in Arm A compared with Arm B. Histological clearance occurred in five of eight patients (63%) randomized to ingenol mebutate gel, 0.05% in Arm A., Conclusions: Two applications of ingenol mebutate gel, 0.05%, are safe and have efficacy in patients with superficial basal cell carcinoma.

Background: Data suggest that photodynamic therapy using topical methyl aminolevulinate (MAL PDT) may be a noninvasive alternative to excisional surgery for nodular basal cell carcinoma (BCC). In the studies described here, we investigated the histologic response, tolerability, and cosmetic outcome with MAL PDT for primary nodular BCC (or= 50% reduction in greatest diameter) at 3 months were re-treated (21%). Treatment sites were excised at 3 months (clinical nonresponders) or 6 months (clinical responders) after the last treatment., Results: Histologically verified lesion complete response rates were higher with MAL PDT than with placebo [73% (55/75) vs. 27% (20/75)]. Treatment was most effective for facial lesions (89% complete response). Cosmetic outcome was good or excellent in 98% of evaluable, completely responding lesions treated with MAL PDT., Conclusion: Although longer follow-up studies are required, these promising data indicate the potential of topical MAL PDT as a noninvasive treatment alternative for nodular BCC.

We report on the preparation, atomic resolution imaging, and element selective damage mechanism in atomically thin boron nitride membranes. Flakes of less than 10 layers are prepared by mechanical cleavage and are thinned down to single layers in a high-energy electron beam. At our beam energies, we observe a highly selective sputtering of only one of the elements and predominantly at the exit surface of the specimen, and then subsequent removal of atoms next to a defect. Triangle-shaped holes appear in accordance with the crystallographic orientation of each layer. Defects are compared to those observed in graphene membranes. The observation of clean single-layer membranes shows that hexagonal boron nitride is a further material (in addition to graphene) that can exist in a quasi-two-dimensional allotrope without the need for a substrate.

The sap of the plant Euphorbia peplus is a traditional remedy for skin conditions, including actinic keratosis. The active constituent of the sap is ingenol mebutate (ingenol-3-angelate), formerly known as PEP005. This randomized, double-blind, vehicle-controlled, phase IIa study investigated the safety (and secondarily the efficacy) of two applications of ingenol mebutate gel in 58 patients with biopsy-confirmed actinic keratosis. Five preselected lesions were treated with ingenol mebutate gel, 0.0025%, 0.01% or 0.05%, or vehicle gel, on days 1 and 2 (Arm A) or days 1 and 8 (Arm B). There were no significant differences in tolerability or efficacy between Arms A and B. Treatment was well tolerated. The most common local skin responses were dose-related erythema, flaking/scaling/dryness and scabbing/crusting. Efficacy was greatest with ingenol mebutate gel, 0.05%, which resulted in complete clinical clearance of 71% of treated lesions (P < 0.0001 vs vehicle gel). In addition, 67% of patients treated with ingenol mebutate gel, 0.05% had clinical clearance of at least four of five treated lesions (P = 0.0185 vs vehicle gel). Ingenol mebutate gel is being developed as a short-course topical therapy for actinic keratosis and non-melanoma skin cancer.

A 22-year-old woman presented with recurrent non-ulcerating skin nodules overlying the great saphenous vein on the anteromedial lower legs. Histology showed a granulomatous phlebitis, and polymerase chain reaction performed on lesional skin detected DNA specific for Mycobacterium tuberculosis. The lesions resolved with anti-tuberculous therapy. This case may be a further example of nodular granulomatous phlebitis, a phlebitic tuberculid.

We hypothesized that there is a correlation between the magnitude of endothelial-mediated dilation of brachial artery and erectile function in patients. Thus, flow-mediated dilation of the brachial artery (FMD)-used to assess the function of endothelium-was measured in 56 patients (aged approximately 35 years) having erectile dysfunction for 6-12 months. The patients were grouped based on International Index of Erectile Dysfunction: severe (5-10), moderate (11-16), mild to moderate (17-21), and mild (22-25). As compared to the mild group (8.8 +/- 1.7%), FMD was significantly reduced in the mild-to-moderate group (5.7 +/- 1.1%), moderate group (5.3 +/- 0.8%), and severe group (4.4 +/- 0.6%). Also, there was a positive correlation between the magnitude of endothelial and erectile dysfunction. Patients were treated with the 5-phosphodiesterase inhibitor sildenafil, known to elevate vascular cGMP level and thus the vascular efficacy of internal nitric oxide, for 3 to 6 months prior to the study. The mean doses of sildenafil used were as follows: severe group, 100 mg/event; moderate group, 86.1 +/- 21.4 mg/event; mild-to-moderate group, 71.8 +/- 23.2 mg/event; mild group, 25 mg/event. We found a positive correlation between the sildenafil dose requirement and the severity of erectile dysfunction. On the bases on these findings, together with the known mechanism of action of sildenafil, we propose that vascular endothelial dysfunction could contribute to erectile dysfunction and that erectile dysfunction may be an early marker of peripheral vascular disease.

There has been considerable research into the safety and efficacy of topical 5% imiquimod cream for the treatment of skin cancers in recent years, in particular superficial and nodular basal cell carcinomas. However, there are limited long-term follow-up studies. This retrospective study aims to determine the efficacy of 5% imiquimod cream in the treatment of facial basal cell carcinomas over 3 years. Medical records of 12 patients treated with 5% imiquimod cream at a private dermatology practice during 2001 and 2002 were retrospectively reviewed. Target tumours included superficial and nodular basal cell carcinomas, giving a total lesion number of 19. Patients were commenced on a once daily treatment regimen for up to 9 weeks, and given rest periods as required according to the severity of application site reactions. We found that 5% imiquimod cream is an effective treatment option for superficial and nodular basal cell carcinomas, giving a clearance rate of 89.5% at an average of 39 months of follow up.

SUMMARY The short-term efficacy of imiquimod 5% cream for the treatment of primary superficial basal cell carcinoma has been established. This study investigated its efficacy following curettage (without electrodesiccation) for the treatment of primary nodular basal cell carcinoma on the trunk and limbs. Seventeen patients with a total of 34 lesions were enrolled. Curettage was used to de-bulk the lesion and confirm suitable histology. Lesions displaying more aggressive subtypes (such as micronodular or morpheoic components) were excluded. Lesions were treated daily for 6 to 10 weeks with imiquimod 5% cream. Three months post treatment all lesions were excised, and 32 of 34 treated lesions (94%) were histologically clear of basal cell carcinoma. Fourteen of 17 patients rated the cosmetic outcome of treatment as excellent or good. Curettage followed by imiquimod 5% cream is effective for the treatment of primary nodular basal cell carcinoma on the trunk and limbs, and most patients are pleased with the cosmetic outcome.

Skin cancers pose a significant public health problem in high-risk populations. We have prospectively monitored basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) incidence in a Queensland community over a 10-y period by recording newly treated lesions, supplemented by skin examination surveys. Age-standardized incidence rates of people with new histologically confirmed BCC were 2787 per 100,000 person-years at risk (pyar) among men and 1567 per 100,000 pyar among women, and corresponding tumor rates were 5821 per 100,000 pyar and 2733 per 100,000 pyar, respectively. Incidence rates for men with new SCC were 944 per 100,000 pyar and for women 675 per 100,000 pyar; tumor rates were 1754 per 100,000 pyar and 846 per 100,000 pyar, respectively. Incidence rates of BCC tumors but not SCC tumors varied noticeably according to method of surveillance, with BCC incidence rates based on skin examination surveys around three times higher than background treatment rates. This was mostly due to an increase in diagnosis of new BCC on sites other than the head and neck, arms, and hands associated with skin examination surveys and little to do with advancing the time of diagnosis of BCC on these sites as seen by a return to background rates following the examination surveys. We conclude that BCC that might otherwise go unreported are detected during skin examination surveys and thus that such skin cancer screening can influence the apparent burden of skin cancer.

We report the provocation of localized psoriasis at the sites of application of topical imiquimod, possibly evolving into a generalized flare. A patient with pre-existing psoriasis that had been stable for 14 years was treated with imiquimod 5% cream daily for 6 weeks to three superficial basal cell carcinomas. During treatment one of the lesions developed severe local skin reactions necessitating rest periods, and received only 18 applications in 6 weeks. The other two lesions were treated for all 42 days. Psoriasiform changes developed at all three application sites. Nine-and-a-half weeks after completing treatment the patient developed disseminated small psoriatic lesions. Other recognized triggers of psoriasis were not identified. The psoriasis resolved slowly with conventional treatment.

We report the successful use of topical imiquimod 5% cream for extensive multifocal, recurrent (post cryotherapy), biopsy-proven Bowen's disease of the nose. Treatment was applied on a once-a-day regimen, and a total of 32 applications over 9 weeks were used. A florid local skin reaction occurred early in the treatment, necessitating a rest period and decreasing the frequency of application. The Bowen's disease was coexistent with a multifocal superficial basal cell carcinoma (BCC) that had a partial response. Persistent BCC at 4 weeks post treatment was surgically excised. This tumour showed an unusual histological picture, with normal epidermis overlying residual BCC in the papillary dermis. The Bowen's disease remains clinically clear at 12-months follow up.

The finding of mutations in the PTCH gene in both Gorlin's syndrome and sporadic basal cell carcinomas has significantly advanced our understanding of the molecular defects that lead to the formation of these tumours. Knowledge of the specific molecular and functional changes that have taken place in these tumours will help us devise more defined therapies, as well as give us a better understanding of normal molecular pathways involved in skin development and function. The following is a summary of our current understanding of the molecular and cellular biology of basal cell carcinoma.

The authors examined the spatial accumulation of mortality and morbidity of cancer of the prostate of the total as well as age stratified male population of Hungary. Using GIS, a descriptive epidemiological study was carried out examining the spatial differences of mortality on settlement level with 2000 inhabitants by calculating standardized mortality and morbidity ratios. The significance of the difference of mortality and morbidity from the national mean was tested by chi square probe. On the basis of the results a significant excess in mortality was detected in 11 regions of the country. The unfavourable regions cover 11.6% of the territory of the country where 25.6% of the male population live. A significant excess morbidity can be observed in 8 counties. A significant correlation was found between the unfavourable regions of mortality and morbidity (r=0.443, p<0.05). The age-specific analysis of morbidity revealed the highest excess in morbidity in the age group over 70 years accumulating in 3 counties of Transdanubia and in 6 counties of the Great Plain. On the basis of the results of mortality and morbidity analysis according to age and areas the unfavourable regions can be identified where mortality and morbidity from cancer of the prostate accumulates. These studies serve as a basis for intervention strategies.

We have identified a novel mutation within the linker L12 region of keratin 5 (K5) in a family with the Köbner variant of epidermolysis bullosa simplex. The pattern of inheritance of the disorder in this family is consistent with an autosomal dominant mode of transmission. Affected individuals develop extensive and generalized blistering at birth or early infancy but in later years clinical manifestations are largely confined to palmoplantar surfaces. Direct sequencing of polymerase chain reaction products revealed a T to C transition within codon 323 of K5 in affected individuals, resulting in a valine to alanine substitution of the seventh residue within the L12 linker domain. This mutation was not observed in unaffected family members or in 100 K5 alleles of unrelated individuals with normal skin. The other critical regions of K5 and K14 were unremarkable in this family except for common polymorphisms that have been previously described. The valine at position 7 of the L12 domain is absolutely conserved in all type II keratins, and in other intermediate filament subunits as well, which suggests that this residue makes an important contribution to filament integrity. Secondary structure analysis revealed that alanine at this position markedly reduces both the hydrophobicity and the beta-sheet nature of the L12 domain. This is the first report of a mutation at this position in an intermediate filament subunit and reinforces the importance of this region to filament biology.

A case of multiple miliary osteomas of the face arising in a 45-year-old Caucasian female with no history of skin disease is reported. Spontaneous development of numerous asymptomatic, skin-coloured facial papules had occurred over a 3 year period. Originally described in association with long-standing acne vulgaris, multiple miliary osteomas of the face has recently been reported in patients without prior skin disease. The pathogenesis, classification and treatment of this rare condition are discussed.

Oral mucosal pigmentation is an infrequently reported side effect of minocycline. Two patients with minocycline deposition within teeth and bone, demonstrated by fluorescence microscopy, are described. Minocycline is the only tetracycline reported to cause discoloration of the oral mucosa. This may be the result of deposition of an insoluble degradation product of minocycline in the underlying bone. Pigmentation is not necessarily dose-dependent and may take months or years to resolve.

Nickel contact dermatitis appears to be almost exclusively a disease of females despite the increasing exposure of males to nickel. Successful murine models of nickel allergic contact dermatitis have been described. The purpose of this study is to investigate the kinetics and specificity of the response in this model and to examine if any differences exist between male and female. Mice were sensitised epicutaneously with nickel sulphate in aqueous solution of varying concentration, volume and duration of application. Following intradermal challenge, dose dependent response kinetics which approximated linearity were demonstrated upto the point of toxicity. Sensitised mice were challenged with Cobaltous chloride, Chromic chloride and Cupric sulphate and demonstrated no evidence of cross sensitivity to cobalt or chrome. Copper produced an irritant response making interpretation difficult. Earlier and stronger responses were observed in female mice, however these differences fell short of statistical significance. The results of the present study therefore establishes a reliable model for nickel hypersensitivity, that demonstrates both specificity and dose dependent kinetics without significant sex differences.

Glucagonoma Syndrome is a rare syndrome comprising hyperglucagonemia, diabetes mellitus, necrolytic migratory erythema and hypoaminoacidemia in the setting of a glucagon producing, alpha cell tumour of the pancreas. We report a case of Glucagonoma Syndrome palliatively treated successfully with octreotide. In addition to classical clinical and biochemical findings, this patient also had a Glomus Jugulare tumour, and Empty Sella Syndrome and demonstrated an unusual pattern of plasma lactate dehydrogenase isoenzymes, features not previously reported in this syndrome.

Four cases of acute gangrenous inflammation of the male genitals are discussed, after a brief review of the literature, with reference to the authors' own experience. In addition to dermal and fascial necrosis the disease causes severe sepsis and shock. Characteristics include rapid progression, occasionally in a matter of hours, and high rate of mortality. Attention is called to the importance of early surgical intervention and to the difficulties in combatting the septic shock.

When prophylactic antibiotics are used in abdominal surgery it is customary to give the first dose before the operation. Whilst intra-operative antibiotics may be effective in elective surgery, there may be an advantage to starting pre-operatively when there is already an infective focus such as appendicitis. Antibiotics started pre-operatively (group P) have been compared with antibiotics started after initial abdominal exploration (group T). Three intravenous doses of 500 mg metronidazole plus 1 g cephazolin were given in a randomized, double-blind study of 700 emergency and elective high-risk abdominal operations. Antibiotic plasma concentrations at the end of the operation were significantly lower in group P but lay well within the therapeutic range. Wound infection rates, which included minor and delayed infections, were similar in both groups (group P, 57 of 342, 16.7 per cent; group T, 55 of 358, 15.4 per cent; 95 per cent confidence intervals for the difference being -4.1 to +6.7 per cent. In appendicitis, wound infection rates were 12.1 and 13.9 per cent for groups P and T respectively. However, non-fatal deep sepsis was more common in group P (nine cases) than in group T (two cases) (chi 2 = 4.9, P less than 0.05). Postoperative infection was twice as common in obese patients whose body mass index (BMI) was greater than or equal to 26 (39 of 132, 30 per cent) than in thin patients whose BMI was less than 24 (41 of 288, 14 per cent; chi 2 = 13.8, P less than 0.001). This study failed to show any advantage to starting antibiotics pre-operatively, even in appendicitis.